Myestheria gravis (MG) is an antibody-mediated, T-cell-dependent autoimmune disease caused by reduction in the number of acetylcholine receptors (AChR) at the neuromuscular junction. It is one of the best characterized autoimmune diseases, with well defined pathology and clear surrogate markers (anti- AChR antibody, electromyography). Anergen, Inc. has patented the use of soluble major histocompatibility complex molecules (MHC) binding peptides of important autoimmue antigen as therapeutics to treat autoimmunity. MG is the type of T cell mediated disease for which this therapeutic approach may be valuable, but there is no consensus on the identity of immunodominant AChR T cell epitopes. The specific aim of this proposal is to determine whether T lymphocyte recognition of dominant AchR epitopes occurs in individuals or in patients population. If a limited number of peptides can be identified, it will pave the way to the development of an MHC-based therapy for MG. The short term goals of this Phase I proposal are: (a) identification of AChR epsilon peptides with high affinity for MG-associated HLA-DR alleles; (b) identification of immunodominant AChR alpha and AChR epsilon peptides by an improved ELISPOT assay of MG patient T cells. The long term goal that will be addressed in a Phase II proposal is to develop an antigen- specific therapeutic for MG. PROPOSED COMMERCIAL APPLICATION: AchR derived immunodominant autoantigenic peptide, identified in this project will be used to develop commercially viable MHC-peptide complex therapeutic for the treatment of myestheria gravis.